INDIRECT MECHANISMS CONTRIBUTE TO BIOLOGICAL EFFECTS PRODUCED BY DECAY OF DNA-INCORPORATED I-125 IN MAMMALIAN-CELLS IN-VITRO - DOUBLE-STRAND BREAKS

We have examined whether nuclear DNA can be protected from double-stra nd breaks (DSBs) induced by decay of the Auger-electron-emitting radio nuclide I-125. Decays were accumulated at 0.3 degrees C in Chinese ham ster V79 cells suspended in isotonic buffer containing 0.1 M EDTA in t he presence or absence of 10% dimethyl sulfoxide (DMSO). DSBs were mea sured by the neutral elution method (pH 9.6) and quantified as strand scission factors. DMSO was shown to protect DNA from DSBs caused by th e decay of DNA-incorporated I-125. The dose modification factor (DMF) for this radionuclide decreases as a function of I-125 decays (389 to 4,100 decays, DMF = 2.5 to 1.3). Extrapolation of the curve for the DM F indicates that at similar to 15,000 decays/cell, a DMF of 1 would be obtained. Experiments using large numbers of I-125 decays confirmed t hese extrapolations. For induction of DSBs by Cs-137 gamma rays, the D MF also decreases with dose (50 to 290 Gy, DMF = 2.7 to 1.5). However, extrapolation of the curve for the DMF indicates that protection does not cease at higher doses. The data show that, at the same level of d amage, DMSO can protect against gamma-ray-induced DSBs 1.35-fold more efficiently than against DSBs caused by the decay of DNA-incorporated I-125. It appears that when I-125 is incorporated into DNA, chromatin structure fosters some DSB formation by an indirect mechanism(s) and t hat more than one DSB is generated per decaying atom. (C) 1998 by Radi ation Research Society.